Osteoporosis

THE ESSENTIALS

- Annual costs of osteoporotic fractures are £1.7 billion in the UK.

- A 50-year-old woman has a 50 per cent chance of a future fracture.

- NICE guidance for secondary prevention of fracture is now available.

- HRT is no longer recommended for prevention of osteoporotic fracture.

- Investigations might be needed to exclude secondary causes.

1. EPIDEMIOLOGY OF OSTEOPOROTIC FRACTURE

Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone tissue, which leads to increased bone fragility and susceptibility to fracture.

Osteoporotic fractures occur at areas with large amounts of trabecular bone, including the proximal femur, vertebrae and distal radius.

Incidence of fractures A recent study estimated that a 50-year-old woman had a risk of 53.2 per cent of sustaining a fracture at some point in the future. For a man of the same age, the risk was 20.7 per cent.

For a woman, the lifetime risks were 16.6 per cent for fracture of the radius or ulna, 11.4 per cent for the femur or hip, and 13.1 per cent for a vertebral body. The corresponding figures for a man were 2.9 per cent, 3.1 per cent and 1.2 per cent respectively.

Among women, the risk of sustaining any fracture in the next 10 years increased from 9.8 per cent at age 50 to 21.7 per cent at age 80. In contrast, this risk remained fairly stable in men, increasing from 7.1 per cent at age 50 to 8 per cent at age 80.

All osteoporotic fractures are associated with significant morbidity, but hip and vertebral fractures increase mortality as well. In the UK the annual cost to the healthcare system from osteoporotic fracture has been estimated at £1.7 billion and is rising faster than the general rate of inflation. Hip fractures account for over a third of the total figure.

Variations in risk Hip fracture incidence rates might vary widely within the same country.

Age- and sex-adjusted hip fracture rates are generally higher in white than in black or Asian populations. The highest recorded rates of hip fracture, after age-adjustment, come from Sweden and the northern US.

Intermediate rates are found in Asian populations, and African peoples have the lowest rates. People of African origin have similar hip fracture rates, irrespective of gender.

Variations in lifestyle factors such as low milk consumption, cigarette smoking, lack of sunlight exposure, low BMI and physical activity might explain some of the difference, but genetic factors might also be important.

Diseases associated with secondary osteoporosis and with falling seem to be a more important cause of hip fractures in men than in women. Epidemiological studies have been impeded by the fact that only about a third of all vertebral deformities noted on radiographs come to medical attention. Only a quarter of vertebral fractures result from falls, and most are precipitated by routine activities such as bending.

About 80 per cent of wrist fractures occur in women. These fractures increase linearly in women from the age of 40, reaching a plateau in the mid-60s. After this, a woman might be more likely to fall on her hip because of deteriorating neuromuscular coordination. In men the incidence remains static, despite a decrease in bone mineral density with age.

A winter peak might reflect falls on icy surfaces. Distal forearm fracture and hip fracture usually follow a fall from standing height or less. The likelihood of falling increases with age, and with many other factors including drugs such as antidepressants and benzodiazepines, and coexistent illness. Physical inactivity might be a risk factor.

About 1 per cent of falls lead to a hip fracture. Falling sideways carries greater risk as there is a direct impact on the greater trochanter and it might not be possible to break the fall with an outstretched hand.

KEY POINTS

- One in five 80-year-old women will sustain a fracture in the next 10 years.

- For men of the same age, the risk is 8 per cent.

- Hip fractures account for more than a third of the annual £1.7 billion cost of osteoporotic fractures in the UK.

- 80 per cent of wrist fractures occur in women.

- About 1 per cent of falls lead to a hip fracture.

2. IDENTIFYING PATIENTS AT RISK OF OSTEOPOROSIS

The main target groups for identification and treatment of osteoporosis are patients who would benefit from primary and secondary prevention. Currently, there are two possible approaches.

A population-based approach would aim to increase the bone density of the whole population, or to screen everyone. The alternative is a case-finding strategy, which aims to identify people at highest risk and treat them.

Population screening for osteoporosis is currently not cost-effective and is not recommended. A case-finding approach is recommended to identify people who are at increased risk or already have osteoporosis (see box right).

In addition, a WHO review is currently under way, which will provide a fracture risk assessment in the form of 10-year fracture risk, expressed as a percentage in men and women according to their age, bone mineral density value, and the presence/ absence of other independent risk factors for fractures, such as a family history of fragility fracture, previous personal fragility fracture, corticosteroid use and smoking. The technical report is expected to be published in mid-2006, and will advise targeting of treatment to those at highest risk of fracture.

Who is at risk?

People who have had a previous fragility fracture are at increased risk of further fracture. Previous vertebral deformities increase the risk of subsequent ones by seven- to 10-fold. This is similar to the increase in risk of hip fracture among people who have already sustained a hip fracture. Older people who have a distal forearm fracture are also at increased risk of subsequent hip or vertebral fracture.

Other groups at increased risk of osteoporosis include women who have had a surgical or natural menopause before the age of 45 or have had pre-menopausal amenorrhoea for more than six months when not pregnant. Women who have had a hysterectomy with at least one ovary conserved before the age of 45 years are also at increased risk.

Other risk factors include current or planned oral corticosteroid use, involving 7.5mg or more of prednisolone per day for at least three months, and a family history of osteoporosis (especially maternal hip fracture).

Predisposing factors include liver disease, alcoholism, malabsorption, thyroid disease, rheumatoid arthritis, anorexia and hypogonadism in men. Some patients with no risk factors may develop osteoporosis.

RISK FACTORS
- Previous fragility fracture.
- Early menopause, hysterectomy or previous long-term amenorrhoea.
- Long-term oral corticosteroid use.
- Family history.
- Predisposing factors include liver disease, alcoholism, thyroid
disease, rheumatoid arthritis and low BMI.

3. WHO SHOULD HAVE A DEXA SCAN?

The gold standard

DEXA scanning is the current 'gold standard' for identifying osteoporosis and predicting future fracture risk. Most DEXA scanning units provide guidelines on appropriate referral. However, a scan should only be requested if the result is likely to change management.

Conditions such as previous vertebral fracture, aortic calcification and osteoarthritis can interfere with the accuracy of scanning. Because of this, results obtained at the hip are most likely to reflect the true bone mineral density.

Diagnostic scan criteria

Women would usually be considered for a diagnostic scan if they had an early surgical or natural menopause (before the age of 45 years), pre-menopausal amenorrhoea for more than six months not due to pregnancy, or a hysterectomy with at least one ovary conserved before the age of 45 years.

Any patient with a previous fragility fracture, height loss or kyphosis, or radiographic evidence of osteopenia would also be considered, as would a patient taking 7.5mg or more of prednisolone daily for three months or more, or a patient with possible secondary osteoporosis (see section 5 below).

Results from DEXA scans are usually reported as a T score and a Z score.

The T score results

The T score provides a comparison with the young adult mean, and relates to absolute fracture risk, while the Z score relates to the patient's relative risk for their age.

A T score of above -1.0 is considered normal, a score between -1.0 and - 2.5 is defined as osteopenia, and a value more negative than -2.5 indicates osteoporosis. A patient who has a T score of 2.5 or less and has had one or more fragility fractures has established osteoporosis.

Any patient with a T score indicating osteopenia (or worse) should be given advice on improving their lifestyle, plus calcium and vitamin D prescriptions as appropriate. Patients who fall into the osteoporotic category should also be considered for further treatment (see section 4).

Key points

- DEXA scans are most accurate at the hip.

- Patients are usually considered for a scan if they have risk factors for osteoporosis, height loss or kyphosis, or X-ray evidence of osteopenia.

- Any patient with a T score of -1 or less should be given advice plus calcium and vitamin D as appropriate.

- A T score of -2.5 or less indicates osteoporosis and additional treatments might be needed.

- Always consider patients taking 7.5mg or more of prednisolone daily for more than three months for a scan.

4. INITIATING AND MONITORING TREATMENT

Educating patients

All patients need to be given education about osteoporosis, lifestyle advice and a review of their calcium and vitamin D intake. Lifestyle measures include stopping smoking, avoiding excessive alcohol intake, taking regular weight-bearing exercise, and avoiding excessive dieting and exercise resulting in amenorrhoea.

Recommended daily intakes for adults for calcium and vitamin D are 700mg and 400IU, respectively.

The NICE technology appraisal regarding secondary prevention of fragility fracture in postmenopausal women was published at the beginning of 2005 (see box, right).

Supplementation

Patients should be supplemented with calcium and vitamin D if necessary.

Age-independent risk factors are: low BMI (<19 kg/m2), family history of maternal hip fracture before age 75, untreated premature menopause, a medical condition associated with bone loss such as chronic inflammatory bowel disease, rheumatoid arthritis, hyperthyroidism or coeliac disease or conditions associated with prolonged immobility.

An unsatisfactory response occurs when a woman has another fragility fracture despite adhering fully to treatment for one year and if there is also evidence of a decline in BMD below her pre-treatment level. Intolerance of bisphosphonates is defined as oesophageal ulceration, erosion or stricture, or severe lower gastrointestinal symptoms that warrant discontinuation of treatment with a bisphosphonate.

The publication of the NICE primary fracture prevention appraisal is expected in April 2006, as is NICE guidance regarding the use of a new agent, strontium ranelate.

Dual agent

Strontium ranelate is classified as a dual action bone agent, that is, it simultaneously promotes bone formation and reduces bone resorption.

Randomised controlled trials have shown a 16 per cent reduction in all non-vertebral fractures; among women at high risk of fracture, a 36 per cent reduction in fracture rate was achieved.

The agent was also associated with a 49 per cent reduction in vertebral fractures.

It is given orally at a dose of 2g daily, preferably at bedtime and two hours after eating. The most common side-effect is gastrointestinal upset.

Of note, strontium becomes part of the hydroxyapatite crystal in bone.

Given the high atomic weight of strontium this makes changes in BMD on treatment hard to interpret.

SUMMARY OF NICE RECOMMENDATIONS ON TREATMENT OPTIONS

Bisphosphonates (alendronate, risedronate and cyclical etidronate) are recommended as treatments for postmenopausal women:

- Aged 75 plus, without a prior DEXA scan.

- Aged 65-74 years, if osteoporosis is confirmed by DEXA scan (T score below -2.5 SD).

- Aged less than 65 years with very low BMD (T score of approximately -3 SD or below) or with confirmed osteoporosis plus one or more additional risk factors (see below).

- Choice of bisphosphonates should be made according to a balance between the drug's effectiveness, tolerability and side-effects in individual patients.

Raloxifene is recommended as an alternative treatment option in women:

- For whom bisphosphonates are contraindicated.

- Who are unable to take bisphosphonates.

- Who have had an unsatisfactory response to or who are intolerant of bisphosphonates.

Teriparatide is recommended as a treatment option in women:

- Who have had an unsatisfactory response to, or who are intolerant of, bisphosphonates; AND

- Who have an extremely low BMD (T score of approximately -4SD or below); OR

- Who have a very low BMD, plus multiple fractures, and one or more additional age-independent risk factors.

5. SECONDARY OSTEOPOROSIS

Secondary causes

Before starting treatment for osteoporosis, it is important to do further investigations where necessary to confirm the diagnosis and identify any secondary causes of the condition. Secondary causes can include hyperparathyroidism, alcohol abuse, hyperthyroidism or hypothyroidism.

It is also important to exclude other diseases and bone conditions that might mimic some of the features of osteoporosis, such as malignancy or osteomalacia.

Other investigations

Investigations that might be needed include an X-ray of the thoracic or lumbar spine to confirm vertebral collapse and exclude bony secondaries. Renal function tests will exclude renal osteodystrophy, and liver function tests will reveal problems such as alcohol abuse.

The ESR will be elevated in a patient with myeloma. In these cases, plasma electrophoresis will be done to confirm the diagnosis.

Levels of calcium, phosphate and alkaline phosphatase are abnormal in patients with osteomalacia or bony secondaries.

Thyroid function tests might be helpful in some cases. Finally, testosterone and sex hormone binding globulin levels might be needed to exclude hypogonadism in men.

Secondary osteoporosis is particularly common in men, and might account for 40-50 per cent of cases.

INVESTIGATIONS
- X-ray of thoracic or lumbar spine.
- Renal function tests.
- Liver function tests.
- ESR.
- Protein electrophoresis if ESR elevated.
- Calcium levels.
- Phosphate levels.
- Alkaline phosphatase measurement.
- Thyroid function tests.
- Testosterone.
- Sex hormone binding globulin.

FURTHER RESOURCES
Further reading
Rheumatic Disease Clinics of North America 2001; 27(1).

WEBSITES
www.nos.org.uk - National Osteoporosis Society website
www.arc.org.uk - Arthritis Research Campaign
www.nice.org.uk - NICE guidance on treatment of fractures

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